Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease

NCT07760909 | Not Yet Recruiting

• 1 other identifier: 260832
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This prospective, single-center pilot study will evaluate metabolic flux dysregulation in adults with obesity and suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) who are scheduled for protocol-eligible bariatric surgery at Vanderbilt University Medical Center. Participants will undergo research assessments before surgery, during the planned bariatric surgery encounter, and approximately 6 months after surgery. The study uses non-radioactive stable isotope tracer infusions, serial blood sampling, abdominal MRI/MRE, and research tissue specimens collected only during clinically planned bariatric surgery to quantify hepatic and extrahepatic metabolic fluxes. The primary objective is to determine how hepatic citric acid cycle flux and related metabolic pathways change after bariatric surgery and how these metabolic measures relate to liver fat, liver stiffness, and biopsy-graded MASLD/MASH severity.

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease; Metabolic Dysfunction-Associated Steatohepatitis; Obesity; Bariatric Surgery

Keywords

MASLD; MASH; metabolic flux analysis; stable isotope tracer; bariatric surgery; Roux-en-Y gastric bypass; sleeve gastrectomy; liver fat; magnetic resonance elastography; citric acid cycle; gluconeogenesis; free fatty acid turnover

Outcome Measures

Primary Outcomes (1)

• Change in hepatic citric acid cycle flux after bariatric surgery

  Change in hepatic citric acid cycle flux estimated from stable isotope enrichment patterns, including \[¹³C₃\]lactate-based measurements, before bariatric surgery and approximately 6 months after surgery.

  Baseline/day of surgery to approximately 6 months post-surgery

Secondary Outcomes (11)

• Change in hepatic gluconeogenic flux

  Baseline/day of surgery to ~6 months

• Change in endogenous glucose production

  Baseline/day of surgery to ~6 months

• Change in free fatty acid turnover

  Baseline/day of surgery to ~6 months

• Change in lactate turnover / lactate-related flux

  Baseline/day of surgery to ~6 months

• Liver fat by MRI-PDFF

  Baseline to ~6 months

Study Arms (1)

Bariatric Surgery Participants Undergoing Metabolic Flux Assessment

EXPERIMENTAL

Adults scheduled and clinically cleared for protocol-eligible bariatric surgery at VUMC will undergo research MRI/MRE, blood collection, non-radioactive stable isotope tracer infusions, and intraoperative research tissue collection during planned bariatric surgery, followed by repeat noninvasive metabolic assessment approximately 6 months after surgery.

Procedure: Bariatric surgery; Other: Stable isotope tracer infusion; Diagnostic Test: MRI/MRE; Procedure: Research tissue collection during planned bariatric surgery

Interventions

Bariatric surgery PROCEDURE

Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.

Also known as: Roux-en-Y-gastric byass, sleeve gastrectomey

Bariatric Surgery Participants Undergoing Metabolic Flux Assessment

Stable isotope tracer infusion OTHER

Intravenous non-radioactive stable isotope tracers administered for research measurement of metabolic flux: \[¹³C₃\]lactate, \[6,6-²H₂\]-D-glucose, and \[9,9-²H₂\]palmitate.

Bariatric Surgery Participants Undergoing Metabolic Flux Assessment

MRI/MRE DIAGNOSTIC_TEST

Abdominal MRI proton density fat fraction and magnetic resonance elastography to assess hepatic fat and stiffness before surgery and approximately 6 months after surgery.

Also known as: magnetic resonance imaging, magnetic resonance elastography

Bariatric Surgery Participants Undergoing Metabolic Flux Assessment

Research tissue collection during planned bariatric surgery PROCEDURE

Liver, omentum, subcutaneous adipose tissue, and skeletal muscle specimens collected only during clinically planned bariatric surgery and only if safe in the surgeon's judgment.

Bariatric Surgery Participants Undergoing Metabolic Flux Assessment

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled and clinically cleared for protocol-eligible bariatric surgery at Vanderbilt University Medical Center.
• BMI ≥40 kg/m², or BMI \>35 kg/m² with at least one obesity-associated comorbidity, such as type 2 diabetes, cardiovascular disease, hypertension, hyperlipidemia, obstructive sleep apnea, MASLD, osteoarthritis, or polycystic ovarian syndrome.
• Able and willing to complete study procedures, including informed consent, questionnaires, blood draws, MRI/MRE imaging, stable isotope tracer infusion, and research tissue collection during planned bariatric surgery.
• Able to provide informed consent in English.

You may not qualify if:

• Contraindication to MRI/MRE, including implanted cardiac defibrillator, pacemaker, or other MRI-incompatible implanted device.
• Prior gastric or intestinal surgery, pancreatic surgery, or other prior surgery that, in the judgment of the study team or bariatric surgeon, would interfere with study procedures or outcome interpretation.
• Active cancer or ongoing cancer treatment.
• Presence or history of HIV infection.
• Alcohol use above study-defined limits: more than 14 alcoholic drinks per week for men or more than 7 alcoholic drinks per week for women, or illicit drug use that would interfere with safe participation or interpretation of study results.
• Anemia or other hematologic condition that would increase risk from study blood collection.
• Abnormal ECG or clinically significant cardiovascular finding that would increase risk from study procedures.
• Impaired renal function or other clinically significant condition that would increase risk from study participation.
• Known Wilson's disease, alpha-1 antitrypsin deficiency, hemochromatosis, or other non-MASLD chronic liver disease that would confound interpretation of study outcomes.
• Any medical, surgical, or safety condition that, in the judgment of the PI, clinical co-investigator, CRC staff, anesthesia team, or bariatric surgeon, would make participation unsafe or interfere with completion of study procedures.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

MeSH Terms

Conditions

Obesity; Fatty Liver

Interventions

Bariatric Surgery; Magnetic Resonance Imaging; Elasticity Imaging Techniques

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography

Study Officials

• Charles R Flynn, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charles R Flynn, PhD

CONTACT

615-343-8329; MASLD.research@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Bariatric surgery

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: August 12, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): January 1, 2060
• Last Updated: August 12, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available within one year after study end.